Article tools
Author information
Published in Volume 99, Issue 2 (January 15,1997)
J. Clin. Invest. 99(2): 200-208 (1997). doi:10.1172/JCI119148.
Copyright © 1997, The American Society for Clinical Investigation.

Research Article

Impaired arterial neointima formation in mice with disruption of the plasminogen gene.

P Carmeliet, L Moons, V Ploplis, E Plow and D Collen

Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium.

Published January 15, 1997

To define the role of plasminogen (Plg) in the smooth muscle cell response after arterial wall injury, neointima formation was evaluated after electric injury of the femoral artery in plasminogen-deficient (Plg-/-) mice. The injury destroyed all medial smooth muscle cells, denuded the injured segment of intact endothelium, and induced transient platelet-rich mural thrombosis. In wild-type (Plg+/+) mice, vascular wound healing was characterized by lysis of the thrombus, transient infiltration of inflammatory cells, and progressive removal of necrotic debris and thrombosis. Topographic analysis revealed repopulation of the media and accumulation in the neointima of smooth muscle cells originating from the noninjured borders, which progressed into the necrotic center. In Plg-/- mice, wound healing was significantly impaired with delayed removal of necrotic debris, reduced leucocyte infiltration and smooth muscle cell accumulation, and decreased neointima formation. Smooth muscle cells accumulated at the uninjured borders, but failed to migrate into the necrotic center. Proliferation of smooth muscle cells was not affected by Plg deficiency. Evans blue staining revealed no genotypic differences in reendothelialization. Thus, Plg plays a significant role in vascular wound healing and arterial neointima formation after injury, most likely by affecting cellular migration.

This article Copyright © 1997, The American Society for Clinical Investigation.

Articles that cite
this article:

Plasminogen deficiency
V. Schuster, B. HÜgle, K. Tefs
J Thromb Haemost 5(12):2315. [CrossRef]

Suppressed smooth muscle proliferation and inflammatory cell invasion after arterial injury in elafin-overexpressing mice
Syed H.E. Zaidi, Xiao-Mang You, Sorana Ciura, Stacey O’blenes, Mansoor Husain, Marlene Rabinovitch
J Clin Invest 105(12):1687. [CrossRef]

The plasminogen activation system enhances brain and heart invasion in murine relapsing fever borreliosis
Joseph A. Gebbia, Juan Carlos Garcia Monco, Jay L. Degen, Thomas H. Bugge, Jorge L. Benach
J Clin Invest 103(1):81. [CrossRef]

The role of plasminogen in angiogenesis in vivo
C.-W Oh, J Hoover-plow, E. F Plow
J Thromb Haemost 1(8):1683. [CrossRef]

The status of plasminogen activator inhibitor-1 as a therapeutic target
Peter Charlton
Expert Opin Invest Drugs 6(5):539. [CrossRef]

The Molecular Basis for Anti-Proteolytic and Non-Proteolytic Functions of Plasminogen Activator Inhibitor Type-1: Roles of the Reactive Centre Loop, the Shutter Region, the Flexible Joint Region and the Small Serpin Fragment
Troels Wind, Martin Hansen, Jan K. Jensen, Peter A. Andreasen
bchm 383(1):21. [CrossRef]

Fibroblast growth factor 2 control of vascular tone
Ming Zhou, Roy L. Sutliff, Richard J. Paul, John N. Lorenz, James B. Hoying, Christian C. Haudenschild, Moying Yin, J. Douglas Coffin, Ling Kong, Evangelia G. Kranias
Nat Med 4(2):201. [CrossRef]

Histone H2B as a functionally important plasminogen receptor on macrophages
R. Das, T. Burke, E. F. Plow
110(10):3763. [CrossRef]

In vivo regulation of plasminogen function by plasma carboxypeptidase B
Carmen M. Swaisgood, Detlef Schmitt, Dan Eaton, Edward F. Plow
J Clin Invest 110(9):1275. [CrossRef]

Deficiency of cathepsin S reduces atherosclerosis in LDL receptor–deficient mice
Galina K. Sukhova, Yaou Zhang, Jie-Hong Pan, Youichiro Wada, Takashi Yamamoto, Makoto Naito, Tatsuhiko Kodama, Sotirios Tsimikas, Joseph L. Witztum, Michael L. Lu
J Clin Invest 111(6):897. [CrossRef]

Plasminogen activator/plasmin system in arthritis and inflammation: Friend or foe?
John A. Hamilton
Arthritis Rheum 58(3):645. [CrossRef]

Impact of plasminogen on an in vitro wound healing model based on a perfusion cell culture system
Moyuru Hayashi, Yuichi Matsuzaki, Motoyuki Shimonaka
MOL CELL BIOCHEM 322(1-2):1. [CrossRef]

The role of proteinases in angiogenesis, heart development, restenosis, atherosclerosis, myocardial ischemia, and stroke: Insights from genetic studies
Aernout Luttun, Mieke Dewerchin, Désiré Collen, Peter Carmeliet
Curr Atheroscler Rep 2(5):407. [CrossRef]

Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization
K. Bajou, A. Noël, R.D. Gerard, V. Masson, N. Brunner, C. Holst-hansen, M. Skobe, N.E. Fusenig, P. Carmeliet, D. Collen
Nat Med 4(8):923. [CrossRef]


Vappu Siren, Petteri Kauhanen, Olli Carpen, Michael Luther, Mauri Lepantalo, Antti Vaheri, Riitta Lassila
Blood Coagul Fibrinolysis 14(4):369. [CrossRef]

Plasmin is not protective in experimental renal interstitial fibrosis1
Kristy L. Edgtton, Renae M. Gow, Darren J. Kelly, Peter Carmeliet, A. Richard Kitching
Kidney Int 66(1):68. [CrossRef]

The Potential Influence of Insulin and Plasminogen Activator Inhibitor Type 1 on the Formation of Vulnerable Atherosclerotic Plaques Associated with Type 2 Diabetes
Burton E. Sobel
Proc Assoc Am Phys 111(4):313. [CrossRef]

Vascular development and disorders: Molecular analysis and pathogenic insights
Peter Carmeliet, Desire Collen
Kidney Int 53(6):1519. [CrossRef]

Transgenic mouse models in angiogenesis and cardiovascular disease
Peter Carmeliet, Désiré Collen
J Pathol 190(3):387. [CrossRef]

Functional hierarchy of plasminogen kringles 1 and 4 in fibrinolysis and plasmin-induced cell detachment and apoptosis
Benoit Ho-tin-noe, Gertrudis Rojas, Roger Vranckx, H. Roger Lijnen, Eduardo Angles-cano
FEBS J 272(13):3387. [CrossRef]

Molecular mechanisms of fibrinolysis
Gabriela Cesarman-maus, Katherine A. Hajjar
Br J Haematol 129(3):307. [CrossRef]

A guide to murine fibrinolytic factor structure, function, assays, and genetic alterations
O. Matsuo, H. R. Lijnen, S. Ueshima, S. Kojima, S. S. Smyth
J Thromb Haemost 5(4):680. [CrossRef]

Gene therapy for restenosis
Roy C. Smith, Kenneth Walsh
Curr Cardiol Rep 2(1):13. [CrossRef]

Plasminogen mediates the atherogenic effects of macrophage-expressed urokinase and accelerates atherosclerosis in apoE-knockout mice
M. Kremen, R. Krishnan, I. Emery, J. H. Hu, K. I. Slezicki, A. Wu, K. Qian, L. Du, A. Plawman, A. Stempien-otero
Proc Natl Acad Sci 105(44):17109. [CrossRef]